The overall aim of this project is to analyze the immune response to Toxoplasma gondii in order to define which cellular immune components and parasite target antigens are involved in the control of infection and its breakdown in immunocompromised hosts. Progress was made this year in the following areas: A. In vivo analysis of macrophage functional markers and cytokine expression during reactivation of infection in brain tissue. Reactivation of T. gondii infection in mouse brain was shown to correlate with the disappearance of mRNA's encoding markers of macrophage activation and to be inducible by depletion of TNF-alpha. B. Function of NK cells as alternative effectors of IFN-gamma-dependent resistance. Studies on vaccine-induced resistance in CD8+ deficient mice indicated that NK cells can mediate immunity against T. gondii via the T independent production of IFN-gamma. C. Role of IL-12 in the induction by T. gondii of IFN-gamma from NK cells and the use of the cytokine in the stimulation of resistance in immunodeficient hosts. IL-12 was shown to play a crucial role in the induction of IFN-gamma synthesis in NK cells by T. gondii. Macrophage accessory cells were shown to be the source of the IL-12 induced by the parasite. When administered to immunodeficient mice, IL-12 was shown to induce partial resistance against T. gondii challenge.